title: Predictors of clinically significant drug-drug interactions among patients treated with nonnucleoside reverse transcriptase inhibitor-, protease inhibitor-, and raltegravir-based antiretroviral regimens.
abstract: BACKGROUND
  The Department of Health and Human Services (DHHS) HIV treatment guidelines recommend that antiretroviral regimens for treatment-naïve individuals include at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus either (1) a nonnucleoside reverse transcriptase inhibitor (NNRTI), (2) a protease inhibitor (PI), or (3) raltegravir, an integrase strand transfer inhibitor. Differences in drug-drug interaction potential may represent an important differentiating feature when choosing between these regimen types.
  
  
  OBJECTIVE
  To identify risk factors for clinically significant drug-drug interactions (CSDDIs) among patients on NNRTI-, PI-, and raltegravir-based antiretroviral regimens; compare CSDDI risks between these regimen types; and develop a clinical prediction tool for antiretroviral CSDDIs.
  
  
  METHODS
  In this cross-sectional study, outpatient medical records from the HIV clinic at Albany Medical Center Hospital were randomly selected to review patients' current antiretroviral regimens. Patients treated with NNRTI-, PI-, or raltegravir-based regimens were included. Drug therapies were analyzed for interactions using Lexi-Comp drug interaction software. The CSDDIs were defined as either (1) a drug combination that is contraindicated or accompanied by strong precautions per DHHS antiretroviral guidelines or (2) a drug combination that necessitates a medication dose adjustment.
  
  
  RESULTS
  Of the 500 patient records screened, 229 were included. Baseline characteristics were similar between regimen groups, with the exception of comorbidities. In multivariate analyses, variables independently associated with CSDDIs were use of >5 non-antiretroviral medications (prevalence ratio [PR] 1.86; 95% CI 1.31 to 2.64; p<0.001) and regimen type (NNRTI: PR 2.48, PI: PR 4.96, and raltegravir [referent]: PR 1.00; 95% CI 1.79 to 3.44; p<0.001).
  
  
  CONCLUSIONS
  Use of >5 non-antiretroviral medications or a non-raltegravir-based antiretroviral regimen increased the risk of a CSDDI. Our findings help clarify drug interaction risks among NNRTI-, PI-, and raltegravir-based regimen types that should be considered when prescribing antiretroviral therapy.
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors.forename: Nimish
authors.initials: N
authors.lastname: Patel
authors.forename: Sandra
authors.initials: S
authors.lastname: Abdelsayed
authors.forename: Michael
authors.initials: M
authors.lastname: Veve
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D003430:Cross-Sectional Studies; D004334:Drug Administration Schedule; D004347:Drug Interactions; D024882:Drug Resistance, Viral; D005260:Female; D005544:Forecasting; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068898:Raltegravir Potassium; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D011760:Pyrrolidinones; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium